Evaluation of the influences of low dose polybrominated diphenyl ethers exposure on human early retinal development

Increasing evidence in animal models has suggested that polybrominated diphenyl ethers (PBDEs), a class of brominated flame retardants, can cause retinotoxicity. However, data on the influence of PBDE treatment on human retinal development are scarce due to the lack of appropriate models. In the present study, we report the utilization of human embryonic stem cell-derived retinal organoids (hESC-ROs) for toxicity assessment of the most common PBDE congener (BDE-47) during the early stages of retinal development. Exposure to BDE-47 decreased the thickness and area of the neural retina (NR) of hESC-ROs in a dose-and time-dependent manner. Abnormal retinal cell distributions, disordered NR structures, and neural rosette-like structures were found on hESC-ROs after low-level BDE-47 exposure. Moreover, BDE-47 exposure decreased cell proliferation, promoted cell apoptosis, and caused abnormal differentiation. Transcriptomic analysis demonstrated that differentially expressed genes, caused by BDE-47, were enriched in extracellular matrix organization. Metabolomic studies of hESC-ROs revealed significant changes in the metabolism of purine and glutathione after BDE47 exposure for five weeks. This study clarifies the retinotoxicity of low-level BDE-47 treatment and highlights the powerfulness of the hESC-RO model, deepening our understanding of BDE-47-driven human early retina developmental toxicity.

Automated summary

This study utilizes human embryonic stem cell-derived retinal organoids (hESC-ROs) to assess the toxicity of polybrominated diphenyl ethers (PBDEs) on retinal development. The results show that low-level exposure to PBDEs leads to decreased retinal thickness and area, abnormal cell distributions, reduced cell proliferation, increased cell apoptosis, and abnormal differentiation. Transcriptomic and metabolomic analysis further reveal the impact of PBDEs on extracellular matrix organization and metabolism. Overall, this study enhances our understanding of the retinotoxicity of PBDEs during early human retinal development.